biostudies-literatureMayr CHBundesministerium für Bildung und ForschungDeutsche Zentrum für LungenforschungNHLBI NIH HHSHelmholtz AssociationMax-Planck-GesellschaftCordise12871https://www.ebi.ac.uk/biostudies/studies/S-EPMC8033531biostudies-literatureUnknown13(4)The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single-cell transcriptomic and proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single-cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types. Mass spectrometry analysis of lung lavage fluid (n = 124) and plasma (n = 141) proteomes identified distinct protein signatures correlated with diagnosis, lung function, and injury status. A novel SSTR2+ pericyte state correlated with disease severity and was reflected in lavage fluid by increased levels of the complement regulEMBO molecular medicineIntegrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers.PMC8033531874656R01 HL146519Reichenberger FSilbernagel EAdler HBohm SLindner MTheis FJGeyer PEHilgendorff ALeuschner GMann MKneidinger NAngelidis IPrasse AMaurer BSimon LMSchniering JBehr JSingh PSchiller HBMayr CHAnsari MStrunz MEickelberg OfalseIntegrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers.The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single-cell transcriptomic and proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single-cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types. Mass spectrometry analysis of lung lavage fluid (n = 124) and plasma (n = 141) proteomes identified distinct protein signatures correlated with diagnosis, lung function, and injury status. A novel SSTR2+ pericyte state correlated with disease severity and was reflected in lavage fluid by increased levels of the complement regul2021-01-01T00:00:00Z2021 Apr2026-04-16T11:46:23.22Z2022-02-09T16:01:30.122ZS-EPMC80335313365077410.15252/emmm.202012871